In the field of mass spectrometry, time-of-flight (TOF) techniques are well known. Typical descriptions of those techniques and principles of electron beam characteristics are discussed in the following references:
Pierce, J. R., Theory and Design of Electron Beams, 2nd Edition, Van Nostrand, New York (1954). PA0 Sanzone, G., Energy Resolution of the Conventional Time-of-Flight Mass Spectrometer, The Review of Scientific Instruments, Volume 41, Number 5, 741-2 (May, 1970). PA0 de Heer, W. A., P. Milani, Large Ion Volume Time-of-Flight Mass Spectrometer with Position- and Velocity-Sensitive Detection Capabilities for Cluster Beams, Rev. Sci. Instrum., Volume 62, No. 3, 670-7 (March, 1991).
Matrix-assisted laser desorption ionization (MALDI) is a "soft" ionization technique for introducing very large delicate molecules such as proteins into a mass spectrometer without fragmentation. M. Karas and F. Hillenkamp, Matrix Assisted Laser Desorption Ionization, Anal. Chem. 60, 2299 (1988) describe the method. Using the MALDI technique, molecular samples to be investigated are laid down on a matrix material which absorbs light at the frequency of a particular pulsed laser. When the pulsed laser is focused on the sample, the energy of each pulse is absorbed largely by the matrix. A plume of matrix fragments and ions carries the sample molecules into the vacuum in a largely undisturbed state. A certain fraction of these become ionized due to charge exchange or absorption of energy from nearby matrix fragments. If this takes place in the ion source region of a mass spectrometer it is possible to measure the masses of the sample ions. The method is particularly suited to time-of-flight mass spectrometry since it is inherently a pulsed method. Numerous researchers have built MALDI/LDI time-of-flight mass spectrometers and approximately ten instrument companies offer such instruments. Unlike the present invention, however, none are specifically designed for automation of MALDI/LDI measurements.
Accordingly, it is an object of the present invention to provide a matrix-assisted laser desorption ionization/laser desorption ionization (MALDI/LDI) time of flight mass spectrometer (TOF-MS) constructed in such a manner as to facilitate automated measurement of samples placed therein on a sample plate.
It is also an object of the present invention to provide such a MALDI/LDI TOF-MS which is provided with a sample changer designed to manipulate a microtiter plate defining a plurality of sample wells disposed in a matrix such as an 8.times.12 array dimensionally configured according to industry standards for other analytical equipment.
Another object of the present invention is to provide such a mass spectrometer which further includes a sample imaging system capable of storing sample images in computer memory and displaying such images on a computer monitor with mass spectral and other data.
A further object of the present invention is to provide such a mass spectrometer wherein a sample entry system is carried within an illuminated work shelf.
Still yet another object of the present invention is to provide a MALDI/LDI TOF-MS which is provided with control electronics and software for permitting feedback control of the sample changer and the mass spectrometer, as well as any associated external instruments, based on analysis by the instrument computer, of sample images, mass spectra, or other available data generated by the instrument itself or by the external instrumentation.
Further, it is an object of the present invention to provide a MALDI/LDI TOF-MS having an ion source employing a ground voltage configuration.